MicroRNA-214-3p inhibits proliferation and cell cycle progression by targeting MELK in hepatocellular carcinoma and correlates cancer prognosis.
MicroRNA-214-3p inhibits proliferation and cell cycle progression by targeting MELK in hepatocellular carcinoma and correlates cancer prognosis.
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DOI：
10.1186/s12935-017-0471-1
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发表时间：
2017
影响因子：
5.8
通讯作者：
Wang S
中科院分区：
文献类型：
--
作者：
Li Y;Li Y;Chen Y;Xie Q;Dong N;Gao Y;Deng H;Lu C;Wang S
MicroRNAs被认为是多种生物途径中潜在的调节因子，有助于癌症的诊断和预后。最近的研究发现，microRNA-214-3p(miR-214-3p)与多种肿瘤相关。然而，miR-214-3p在肝细胞癌中的生物学功能及其与肝移植后肝细胞癌预后的关系尚不清楚。本研究旨在阐明miR-214-3p在调节细胞增殖和凋亡中的功能意义及其对肝细胞癌患者临床预后的预测。采用定量逆转录聚合酶链式反应(qRT-PCR)检测98例肝癌患者和3株肝癌细胞株miR-214-3p的表达，探讨miR-214-3p的表达与临床病理特征的关系。分别用增殖实验和流式细胞仪检测miR-214-3p对细胞增殖和凋亡的影响。用荧光素酶报告基因检测miR-214-3p的直接靶基因。分别用增殖实验和流式细胞仪检测miR-214-3p对细胞增殖和凋亡的影响。用荧光素酶报告基因检测miR-214-3p的直接靶基因。结果显示：miR-214-3p在原发性肝癌组织中的表达低于正常肝组织，在复发肝癌组织中的表达低于无复发对照组(P<0.001)。低miR214-3p水平与较差的总体生存率(对数等级P=0.003)和无复发生存率(对数等级P=0.007)相关。此外，miR-214-3p前体基因可抑制细胞增殖，使细胞周期停滞于G1期，促进细胞凋亡。进一步的研究表明，miR-214-3p可以通过直接与Melk-3‘-UTR结合来调节其靶基因母体胚胎亮氨酸拉链酶(Melk)。MIR-214-3p通过直接下调Melk的表达来抑制肝癌的进展，为肝癌患者的治疗和预后提供了潜在的治疗靶点。
MicroRNAs are considered as potential regulators in various biological pathways and contribute to the diagnosis and prognosis of cancers. MicroRNA-214-3p (miR-214-3p) was proved to be correlated with various cancers in recent studies. However, the biological functions of miR-214-3p in hepatocellular carcinoma (HCC) and its association with the prognosis of HCC after liver transplantation are still unevaluated. Here we intended to elucidate the functional implication of miR-214-3p in regulation of cell proliferation and apoptosis and its potential prediction of clinical prognosis of HCC patients. Expressions of miR-214-3p in 98 HCC patients and three HCC cell lines were detected by quantitative reverse transcription PCR (qRT-PCR) to explore the association of miR-214-3p expression and clinicopathological characteristics. The effects of miR-214-3p on cell proliferation and apoptosis were examined by proliferation and flow cytometry assay, respectively. The direct target gene of miR-214-3p was also detected by luciferase reporter assay. The effects of miR-214-3p on cell proliferation and apoptosis were examined by proliferation and flow cytometry assay, respectively. The direct target gene of miR-214-3p was also detected by luciferase reporter assay. The results showed that miR-214-3p expression was downregulated in primary HCC samples compared with normal liver tissues, and was decreased in HCC recurrence species compared with non-recurrence controls (P = 0.001). Low miR-214-3p level was associated with poor overall survival (OS) (Log rank P = 0.003) and recurrence-free survival (RFS) (Log rank P = 0.007). Moreover, miR-214-3p precursor transfection resulted in decreased cell proliferation, cell cycle arrest at G1 phase, and enhanced cell apoptosis in HepG2 and HUH-7 cells. Further investigation showed that miR-214-3p could regulate its target gene maternal embryonic leucine zipper kinase (MELK) by directly binding to MELK-3′-UTR. miR-214-3p suppresses HCC progression by directly down-regulating MELK expression, indicating a potential therapeutic target for the treatment and prognosis of HCC patients.
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影响因子：
--
作者：
Kinose Y;Sawada K;Nakamura K;Kimura T
通讯作者：
Kimura T
影响因子：
4.1
作者：
Wright, LM;Maloney, W;Osdoby, P
通讯作者：
Osdoby, P
破骨细胞 miR-214 靶向 TRAF3，促进乳腺癌的溶骨性骨转移。
影响因子：
4.6
作者：
Liu J;Li D;Dang L;Liang C;Guo B;Lu C;He X;Cheung HY;He B;Liu B;Li F;Lu J;Wang L;Shaikh AB;Jiang F;Lu C;Peng S;Zhang Z;Zhang BT;Pan X;Xiao L;Lu A;Zhang G
通讯作者：
Zhang G
影响因子：
4.2
作者：
Bourassa MW;Ratan RR
通讯作者：
Ratan RR
影响因子：
11.2
作者：
Iorio, MV;Ferracin, M;Croce, CM
通讯作者：
Croce, CM